Microencapsulation Procedures for the Immunoisolation of Wharton’s Jelly Mesenchymal Stem Cells: A Review

  • Stefania Mazzitelli
  • Renata Vecchiatini
  • Letizia Penolazzi
  • Elisabetta Lambertini
  • Roberta Piva
  • Claudio NastruzziEmail author
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 4)


The entrapment of cells is one of the most promising and usefulness tool in tissue transplantation and regenerative medicine. Cell encapsulation procedures allow the physical isolation of cells from the surrounding environment, after their transplantation and the maintenance of the normal cellular physiology. In this paper, different microencapsulation procedures for Wharton’s Jelly Mesenchymal Stem Cells (WJMSCs) are reported, including coaxial bead generator, vibrating-nozzle procedure and microfluidic based approach. The produced microcapsules were characterized by excellent morphological characteristics and a very narrow size distribution. The experiments demonstrated that the microencapsulation procedure did not alter the morphology, viability and osteogenic differentiation of the enveloped WJMSCs. In conclusion, the encapsulation technologies, here presented, represent a promising strategy for the possible in vivo applications of WJMSCs in tissue engineering and biomedicine.


Immunoisolation Cell encapsulation Wharton’s Jelly Mesenchymal Stem Cells 


  1. Anzalone R, Lo Iacono M, Corrao S, Magno F, Loria T, Cappello F, Zummo G, Farina F, La Rocca G (2010) New emerging potentials for human Wharton’s Jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity. Stem Cells Dev 19:423–438PubMedCrossRefGoogle Scholar
  2. Bakeine GJ, Bertolotti A, Latina M, Congiu T, Prati U, Roveda L, Trotta F, Tormen M, Di Fabrizio E, Carlini G, Facoetti A, Nano R (2007) Surface properties and implantation site affect the capsular fibrotic overgrowth. J Biomed Mater Res A 83:965–969PubMedGoogle Scholar
  3. Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36:568–584PubMedCrossRefGoogle Scholar
  4. Borgatti M, Mazzitelli S, Breveglieri G, Gambari R, Nastruzzi C (2010) Induction by TNF-α of IL-6 and IL-8 in cystic fibrosis bronchial IB3-1 epithelial cells encapsulated in alginate microbeads. J Biomed Biotechnol 2010:1–11CrossRefGoogle Scholar
  5. Capretto L, Mazzitelli S, Luca G, Nastruzzi C (2010) Preparation and characterization of polysaccharidic microbeads by a microfluidic technique: application to the encapsulation of Sertoli cells. Acta Biomater 6:429–435PubMedCrossRefGoogle Scholar
  6. Caves JM, Kumar VA, Martinez AW, Kim J, Ripberger CM, Haller CA, Chaikof EL (2010) The use of microfiber composites of elastin-like protein matrix reinforced with synthetic collagen in the design of vascular grafts. Biomaterials 31:7175–7182PubMedCrossRefGoogle Scholar
  7. Chung JT, Zhang Z (2003) Mechanical characterization of calcium pectinate hydrogel for controlled drug delivery. Chem Ind 57:611–616CrossRefGoogle Scholar
  8. Conget PA, Minguell JJ (1999) Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181:67–73PubMedCrossRefGoogle Scholar
  9. De Bruyn C, Najar M, Raicevic G, Meuleman N, Pieters K, Stamatopoulos B, Delforge A, Bron D, Lagneaux L (2010) A rapid, simple, and reproducible method for the isolation of mesenchymal stromal cells from Wharton’s Jelly without enzymatic treatment. Stem Cells Dev 20:547–555PubMedCrossRefGoogle Scholar
  10. Fallarino F, Luca G, Calvitti M, Mancuso F, Nastruzzi C, Fioretti MC, Grohmann U, Becchetti E, Burgevin A, Kratzer R, Van Endert P, Boon L, Puccetti P, Calafiore R (2009) Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone. J Exp Med 206:2511–2526PubMedCrossRefGoogle Scholar
  11. Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton’s Jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24:115–124PubMedCrossRefGoogle Scholar
  12. Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88PubMedCrossRefGoogle Scholar
  13. Huang Y, Yang J, Wang C, Lee S (2010) Dental stem cells and tooth banking for regenerative medicine. J Exp Clin Med 2:111–117CrossRefGoogle Scholar
  14. Jen AC, Wake MC, Mikos AG (1996) Review: hydrogels for cell immobilization. Biotechnol Bioeng 50:357–364PubMedCrossRefGoogle Scholar
  15. Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A (2007) Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells 25:319–331PubMedCrossRefGoogle Scholar
  16. Lewis AS, Colton CK (2007) Engineering challenges in immunobarrier device development. Princ Tissue Eng 3:405–418CrossRefGoogle Scholar
  17. Lim GJ, Zare S, Van Dyke M, Atala A (2010) Cell microencapsulation. Adv Exp Med Biol 670:126–136PubMedCrossRefGoogle Scholar
  18. Luca G, Calvitti M, Nastruzzi C, Bilancetti L, Becchetti E, Angeletti G, Mancuso F, Calafiore R (2007) Encapsulation, in vitro characterization, and in vivo biocompatibility of Sertoli cells in alginate-based microcapsules. Tissue Eng 13:641–648PubMedCrossRefGoogle Scholar
  19. Lund RD, Wang S, Lu B, Girman S, Holmes T, Sauve Y, Messina DJ, Harris IR, Kihm AJ, Harmon AM, Chin FY, Gosiewska A, Mistry SK (2007) Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells 25:602–611PubMedCrossRefGoogle Scholar
  20. Ma PX (2008) Biomimetic materials for tissue engineering. Adv Drug Deliv Rev 60:184–198PubMedCrossRefGoogle Scholar
  21. Madduri S, Papaloïzos M, Gander B (2010) Trophically and topographically functionalized silk fibroin nerve conduits for guided peripheral nerve regeneration. Biomaterials 31:2323–2334PubMedCrossRefGoogle Scholar
  22. Mazzitelli S, Tosi A, Balestra C, Nastruzzi C, Luca G, Mancuso F, Calafiore R, Calvitti M (2008) Production and characterization of alginate microcapsules produced by a vibrational encapsulation device. J Biomater Appl 23:123–145PubMedCrossRefGoogle Scholar
  23. Mazzitelli S, Luca G, Mancuso F, Calvitti M, Calafiore R, Nastruzzi C, Johnson S, Badylak SF (2011a) Production and characterization of engineered alginate-based microparticles containing ECM powder for cell/tissue engineering applications. Acta Biomater 7:1050–1062PubMedCrossRefGoogle Scholar
  24. Mazzitelli S, Borgatti M, Breveglieri G, Gambari R, Nastruzzi C (2011b) Encapsulation of eukaryotic cells in alginate microparticles: cell signaling by TNF-alpha through capsular structure of cystic fibrosis cells. J Cell Commun Signal 5:157–165PubMedCrossRefGoogle Scholar
  25. Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C (2010) Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Adv Biochem Eng Biotechnol 123:29–54PubMedGoogle Scholar
  26. Munarin F, Petrini P, Farè S, Tanzi MC (2010) Structural properties of polysaccharide-based microcapsules for soft tissue regeneration. J Mater Sci Mater Med 21:365–375PubMedCrossRefGoogle Scholar
  27. Noort WA, Kruisselbrink AB, in’t Anker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MHM, Löwik CW, Frederik Falkenburg JH, Willemze R, Fibbe WE (2002) Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 30:870–878PubMedCrossRefGoogle Scholar
  28. Nöth U, Rackwitz L, Steinert AF, Tuan RS (2010) Cell delivery therapeutics for musculoskeletal regeneration. Adv Drug Deliv Rev 62:765–783PubMedCrossRefGoogle Scholar
  29. Penolazzi L, Vecchiatini R, Bignardi S, Lambertini E, Torreggiani E, Canella A, Franceschetti T, Calura G, Vesce F, Piva R (2009) Influence of obstetric factors on osteogenic potential of umbilical cord-derived mesenchymal stem cells. Reprod Biol Endocrinol 7:106–112PubMedCrossRefGoogle Scholar
  30. Penolazzi L, Tavanti E, Vecchiatini R, Lambertini E, Vesce F, Gambari R, Mazzitelli S, Mancuso F, Luca G, Nastruzzi C, Piva R (2010) Encapsulation of mesenchymal stem cells from Wharton’s Jelly in alginate microbeads. Tissue Eng Part C 16:141–155CrossRefGoogle Scholar
  31. Pişkin E (2002) Biodegradable polymeric matrices for bioartificial implants. Int J Artif Organs 25:434–440PubMedGoogle Scholar
  32. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  33. Rabanel JM, Banquy X, Zouaoui H, Mokhtar M, Hildgen P (2009) Progress technology in microencapsulation methods for cell therapy. Biotechnol Prog 25:946–963PubMedCrossRefGoogle Scholar
  34. Saul JM, Williams DF (2011) Hydrogels in regenerative medicine. Princ Regener Med 2:637–661CrossRefGoogle Scholar
  35. Schumacher KM, Phua SC, Schumacher A, Ying JY (2008) Controlled formation of biological tubule systems in extracellular matrix gels in vitro. Kidney Int 73:1187–1192PubMedCrossRefGoogle Scholar
  36. Sheyn D, Mizrahi O, Benjamin S, Gazit Z, Pelled G, Gazit D (2010) Genetically modified cells in regenerative medicine and tissue engineering. Adv Drug Deliv Rev 62:683–698PubMedCrossRefGoogle Scholar
  37. Stewart K, Monk P, Walsh S et al (2003) STRO-1, HOP-26 (CD63), CD49a and SB- 10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell Tissue Res 313:281–290PubMedCrossRefGoogle Scholar
  38. Troyer DL, Weiss ML (2008) Concise review: Whaton Jelly’s-derived cells are primitive stromal cell population. Stem Cells 26:591–599PubMedCrossRefGoogle Scholar
  39. Wang Q, Hub X, Du Y, Kennedy JF (2010) Alginate/starch blend fibers and their properties for drug controlled release. Carbohydr Polym 82:842–847CrossRefGoogle Scholar
  40. Warren Sands R, Mooney DJ (2007) Polymers to direct cell fate by controlling the microenvironment. Curr Opin Biotechnol 18:448–453PubMedCrossRefGoogle Scholar
  41. Woźniak P, Bil M, Ryszkowska J, Wychowański P, Wróbel E, Ratajska A, Hoser G, Przybylski J, Kurzydłowski KJ, Lewandowska-Szumieł M (2010) Candidate bone-tissue-engineered product based on human-bone-derived cells and polyurethane scaffold. Acta Biomater 6:2484–2493PubMedCrossRefGoogle Scholar
  42. Yang J, Yamato M, Nishida K, Ohki T, Kanzaki M, Sekine H, Shimizu T, Okano T (2006) Cell delivery in regenerative medicine: the cell sheet engineering approach. J Control Release 116:193–203PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Stefania Mazzitelli
    • 1
  • Renata Vecchiatini
    • 1
  • Letizia Penolazzi
    • 1
  • Elisabetta Lambertini
    • 1
  • Roberta Piva
    • 1
  • Claudio Nastruzzi
    • 2
    Email author
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of FerraraFerraraItaly
  2. 2.Department of Pharmaceutical SciencesUniversity of FerraraFerraraItaly

Personalised recommendations